Small Molecules Alone or in Combination to Treat Joint Disease and Progress Toward Gene Therapy

The field of biologics for joint disease, specifically articular cartilage injury and osteoarthritis, is one that has stimulated much excitement in the area of orthopaedics. The deficit of growth factors and anticatabolics in joint disease is now a well-recognized problem; however, unraveling the mystery associated with appropriate dose and timing of administration and when these molecules might have their most therapeutic benefits would be the subject of study for decades to come. Further, the technique of how these proteins are enhanced in the joint to result in the greatest influence remains in question. Shall we deliver individual therapeutic proteins in one dose? Shall we enhance the joint environment through biologic solutions that mimic the body's response to injury? Or shall we strive to maintain continued elevated levels of these proteins through gene therapeutic strategies given the timeline of cartilage healing is slow and can sometimes require months to years to heal? The scientific community recognizes that the short half-life of recombinant proteins combined with the question of whether one individual protein can influence healing to the point of augmenting cartilage repair or change the outcome of an osteoarthritic joint leads to asking bigger questions such as what can we attain in multiple combinations of these factors and what is the best way to enhance the joint environment. The evidence is mounting in various studies that increasing levels of anabolic and anticatabolic proteins may have influential therapeutic effects in joints and may change the outcome of cartilage injury and osteoarthritis. This is a summary of the common biologic approaches to enhancing various proteins that may have important effects in joint disease.